Kidney transplantation has extended and improved the quality of life for many patients with end stage renal disease. Most transplants involve genetically non-identical donor to recipient combinations. As a consequence the immune response is a major impediment to successful graft survival, necessitating lifelong treatment with potent immunosuppressive drugs. The donor organ and its complex responses to transplantation is also a major player in all the events determining the clinical events post transplant. Despite recent reductions in the incidence of acute rejection, chronic rejection and immunosuppressive drug side effects are still major causes of graft loss and patient morbidity. In this context, it is essential to advance our understanding of the immune response and the responses of the transplanted organ to both immune and nonimmune injury mechanisms. We will use quantitative shotgun proteomics based on liquid chromatography tandem mass spectrometery to identify protein expression changes in transplanted kidneys and peripheral blood lymphocytes. Proteins will be identified and their expression levels measured relative to samples from patients with well-functioning transplants and no history of rejection. The objectives will be to identify regulatory processes activated or suppressed as a result of the immune response and identify cellular pathways associated with immunity, cell injury and tissue repair. Proteomics data will be integrated with gene expression measurements to gain a more complete view of the rejection process for both protein and gene transcript expression as well as identify and rank 500 gene candidates for complex trait genetics by SNP analysis in Project 3.